The genes in the mouse H-2 major histocompatibility complex determine a diversity of functions associated with immune recognition and reaction. Two of these genes, H-2K and H-2D, encode the major antigens involved in allograft rejection; a feature undoubtedly related to the genetic polymorphism of these H-2 molecules. In addition, these molecules play a role in T-lymphocyte responses to altered cell-surface antigens. These H-2 molecules are integral membrane glycoproteins and are associated on the cell surface and B2-microglobulin. The purpose of this work is to determine the primary structure of these molecules in order that we may better understand their function and mechanism of action. Toward this goal, approximately 40% of the primary structure of the H-2Kb molecule has been elucidated. Structural studies on H-2Db and murine B2-microglobulin have been initiated.